The ability of vitamin A and its synthetic analogs (retinoids) to reverse a potentially premalignant lesion of tracheobronchial epithelium is being studied in organ culture. Keratinized, squamous metaplastic lesions are established in organ cultures of hamster tracheas. Addition of active retinoids causes reversal of these lesions and restoration of healthy mucociliary epithelium. Several new retinoids have been found to be extremely active and relatively free of toxicity, using this experimental system.